The development of increased pulmonary resistance during prolonged bypass pumping is a problem of great importance both clinically and in research concerned with developing artificial circulatory assist devices. From available data, it appears reasonable that leukocyte damage by shear stress or foreign material surface exposure is at least a principal cause of this problem. This research will quantitate the changes in leukocyte function, mechanical properties and morphology caused by in vitro exposure to shear stress and foreign surfaces under precisely viscometric conditions. Also, the leukocyte-platelet interaction caused by mechanical trauma will be studied in great detail. Of special importance will be: a) the effect of antiplatelet agents on reducing leukocyte damage and subsequent leukocyte-platelet aggregation, b) the effect of mechanical trauma on complement and leukocyte-complement interaction, c) the effects of shear stress on lymphocyte function. The relationship obtained between level and type of in vitro leukocyte damage and the rate of inrease in in vivo pulmonary resistance will allow the development of design criteria for circulatory assist devices in terms of permissible levels of shear stress, materials surfaces and drug regimen. Also, these studies may help explain the increased risk of infection seen in hemodialysis and cardio-pulmonary bypass patients.